Carcinogenic, mutagenic, reprotoxic

Results of CMR (Carcinogenic, Mutagenic, Reprotoxic) tests and statement on endocrine disrupting potential. 

A result of the risk assessments was that DEHP, DBP and BBP are toxic for reproduction. Accordingly, they were classified as CMR (carcinogen, mutagen, reprotoxic) substances, category 2 which is reflected in the classification and labelling with R-phrases 60-62 (Tables 12, 13). 

Worker safety (acute and chronic exposure effects, toxicity, carcinogenicity, mutagenicity, reprotoxicity, skin absorption, sensitization, etc.)-... 

More qualitative indicators are also useful absorption through healthy skin, irritation to skin, eyes, and respiratory system, together with sensitization with the following indicators carcinogenic, mutagenic, teratogenic, reprotoxic, and so on. These properties can be summarized by indication of a toxicity class. 

Automatic bans for carcinogenic, mutagenic or reprotoxic (CMR) substances following the restrictions procedure under Directive 76/769 have been excluded (step 2) because these will continue to apply under REACH. The result of the risk criteria evaluation for each substance according to the decision-making matrix is shown in Table 6.1 (step 3). Based on the selection procedure detailed in Section 5.3.2, the most suitable regulatory outcome... 

Authorisation. The use of chemicals considered to be of very high concern would be subject to authorisation. The aim is for such chemicals to be phased out and substituted, unless industry can show that the use presents negligible risk or that it is acceptable, taking into account its socioeconomic benefits, the lack of safer chemicals and measures to minimise exposure. Chemicals of very high concern are likely to include carcinogens, mutagens or reprotoxic substances (CMRs), particularly persistent, bioaccumulative and toxic substances. 

Preparations share the classifications used for substances, but the allocation is dependent either on the results of tests (except for those aimed at carcinogenic, mutagenic, and reprotoxic endpoints) or upon calculations using concentration limits. Unless specific concentration limits are given when the EU agrees the environmental classification for a substance, default concentration limits apply. Those which will apply when the Directive is amended are summarised in Table 6.8. 

The definition of hazardous in combination with substances follows the European Occupational Safety and Health legislation i.e. every substance that has been assigned a so-called H(azard)-statement. Carcinogenicity, Mutagenicity or Reprotoxicity (CMR) are reflected in specific H-statements, but many other types of toxicity exist. This approach should diminish the confusion that arises when hazardous is considered synonym with CMR or, in other situations, even with CMR plus some specific types of toxicity. Let alone if hazardous substances is considered synonym with the therapeutic class of antineoplastics. 

However, the use of the term hazardous substances with regard to pharmacy preparation and recraistitution, is often restricted to carcinogenic, mutagenic and reprotoxic substances. Radiopharmaceuticals and gene therapeutics may be counted under this term as well. The National Institute of Occupational Safety and Health of the US (NIOSH) however also counts substances with a high chronic toxic potential to hazardous substances , see further Sect. 26.3.3. 

The authors of the Pans Appeal then went on to call upon decision-makers at all levels to take a number of radical measures such as banning all products that are certainly or probably carcinogenic, mutagenic or reprotoxic for humans, as well as tightening up the regulations applied to industrial chemicals. 

For instance, as reported by two interviewees, current Health and Safety Executive (HSEO priorities are based on statistics for carcinogenicity, respiratory illnesses and skin disease to the exclusion of mutagenic or reprotoxic effects. 

Amide waxes like stearamide, oleamide, erucamide are subject to extensive risk assessments under the existing chemicals HPV programme in the USA [169]. The available data indicate that there is no mutagenic or reprotoxic potential identified. Repeated dose feeding studies up to 2 years did not reveal a carcinogenic effect. The NOFL was determined to be >7,500 mg kg body weight/day. 

So the term hazardous substances may have different notions. In this chapter the CLP definition is followed meaning that all substances are considered potentially hazardous. Carcinogenic, reprotoxic and mutagenic substances are either noted as such or as a group as CMR. Occupational safety and health care investigates all processes and all substances, to prevent health damage of workers. 

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